Department of Biochemistry, College of Life Science and Biotechnology, World Class University Program of Graduate School, Yonsei Proteome Research Center, Yonsei University, 134 Shinchon-dong, Sudaemoon-ku, Seoul, 120-749, Korea.
J Biochem. 2011 May;149(5):529-38. doi: 10.1093/jb/mvr025. Epub 2011 Mar 9.
Accumulation of lipids inside the cell is primarily caused by disorders of lipid metabolism. S-adenosylmethionine synthetase (SAMS) produces SAM, an important methyl donor in various phospholipid methyltransferase reactions catalysed by phosphoethanolamine N-methyltransferase (PMT-1). A gel-based, quantitative proteomic analysis of the RNA interference (RNAi)-mediated inactivation of the pod-2 gene, which encodes acetyl-CoA carboxylase, showed a substantial down-regulation of SAMS-1. Consequently, RNAi of either sams-1 or pmt-1 caused a significant increase in lipid droplet size in the intestine of Caenorhabditis elegans. Lipid droplets exhibited increased triacylglycerol (TG) and decreased phosphatidylcholine (PC) levels, suggesting a reciprocal relationship between TG and PC regulation. These lipid-associated phenotypes were rescued by choline feeding. Among the five fat metabolism-related genes examined, two genes were highly induced by inactivation of sams-1 or pmt-1: pod-2 and stearoyl-CoA desaturase (fat-7). Thus, both SAMS-1 and PMT-1 were shown to contribute to the homoeostasis of TG and PC levels in C. elegans, which would provide an important survival strategy under harsh environmental conditions.
细胞内脂质的积累主要是由于脂质代谢紊乱引起的。S-腺苷甲硫氨酸合成酶（SAMS）产生 SAM，SAM 是磷酸乙醇胺 N-甲基转移酶（PMT-1）催化的各种磷脂甲基转移酶反应中的重要甲基供体。基于凝胶的 RNA 干扰（RNAi）介导的 pod-2 基因失活的定量蛋白质组学分析显示，SAMS-1 显著下调。因此，sams-1 或 pmt-1 的 RNAi 导致秀丽隐杆线虫肠道中脂滴大小显著增加。脂滴表现出三酰甘油（TG）增加和磷脂酰胆碱（PC）水平降低，表明 TG 和 PC 调节之间存在反向关系。胆碱喂养挽救了这些与脂质相关的表型。在研究的五个与脂肪代谢相关的基因中，有两个基因在 sams-1 或 pmt-1 失活时被高度诱导：pod-2 和硬脂酰辅酶 A 去饱和酶（fat-7）。因此，SAMS-1 和 PMT-1 都被证明有助于秀丽隐杆线虫中 TG 和 PC 水平的体内平衡，这将为在恶劣环境条件下提供重要的生存策略。
